Scientists have identified a mechanism that cells use to repair damage in DNA that is associated with aging and health conditions like cancer and ALS (also known as motor neuron disease). In this study, the researchers determined that a protein known as TEX264 works with two enzymes to identify and consume toxic proteins that can attach to DNA and cause damage. That damaged DNA can lead to a wide range of harmful effects, including an array of diseases. These findings have been reported in Nature Communications.
It may one day be possible to use these findings to develop better treatments for some diseases, and they may provide a better way to target cancer than chemotherapy, the researchers suggested.
"Failure to fix DNA breaks in our genome can impact our ability to enjoy a healthy life at an old age, as well as leave us vulnerable to neurological diseases like motor neuron disease. We hope that by understanding how our cells fix DNA breaks, we can help meet some of these challenges, as well as explore new ways of treating cancer in the future," said study co-author Professor Sherif El-Khamisy, the Co-Founder and Deputy Director of the Healthy Lifespan Institute at the University of Sheffield.
During cell division, the genome has to be replicated. This process can create stress on DNA, which can be relieved by a molecule called topoisomerase 1 (TOP1), which binds to DNA. During this process, an intermediate molecule is formed. While this is supposed to be temporary, it can get stuck that way, which can lead to serious problems for DNA replication. These unresolved intermediates have also been linked to neurodegeneration and cancer. While tyrosyl-DNA phosphodiesterase (TDP1) can sometimes fix the intermediate molecule that is stuck, it doesn't in every case.
This work has shown that TEX264 can fill that gap, as it forms a complex with two other molecules to resolve the intermediate problem.
TEX264 is a protein that generates specialized machinery that can digest toxic proteins affecting our DNA. This research has significantly changed our current understanding of DNA repair in cells, a process that protects us from cancer, accelerated aging, and neurodegeneration, noted corresponding study author Professor Kristijan Ramadan of the University of Oxford."I believe this discovery has a great potential for cancer therapy in the future and we are already pursuing our research in this direction."
"I am very proud of my research team who initially discovered the involvement of TEX264 in DNA repair," added Ramadan.
Sources: University of Sheffield, Nature Communications